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Developing novel tools and technologies to assess the safety and efficacy of cell-based regenerative medicine therapies, focusing on kidney disease


Plan of joint research publications submitted or in preparation.

Plan of joint research publications submitted or in preparation

Report comparing the properties of EVs derived from different MSCs
Theses submitted and PhDs awarded

Theses submitted and PhDs awarded This deliverable might extend beyond month 48

Report on development and implementation of improved clearing & microscopy protocols for analysing intact organs ex vivo

Report on development and implementation of improved clearing microscopy protocols for analysing intact organs ex vivo

Report on development of mathematical tools for analysis of imaging data
Report describing potential mechanism(s) of action of MSCs/EVs.

Report describing potential mechanisms of action of MSCsEVs

Publications and/or patents filed for 4 ESRs in WP1

Publications andor patents filed for 4 ESRs in WP1

Risk:benefit ratio of MSCs as RMTs determined

Riskbenefit ratio of MSCs as RMTs determined

Report indicating effectiveness of mathematical tool for modelling tracer excretion
Report comparing the ability of RMTs to ameliorate injury in vivo
Communication/dissemination plan
Report on development of MSOT/BLI imaging strategy

Report on development of MSOTBLI imaging strategy

Report on composition of novel biomarker panel
Report on development of MRI/BLI imaging strategy

Report on development of MRIBLI imaging strategy

Press release

Press release informing public of RenalToolBox network and its objectives

Report indicating the effect of culture conditions on MSC phenotype
Report comparing properties of A-MSCs,BM-MSCs, UC-MSCs, S-MSCs

Report comparing properties of AMSCsBMMSCs UCMSCs SMSCs

Supervisory board

Supervisory board of the network established.

Publications for 6 ESRs in WP3
Report indicating effectiveness of device, NIRs & biomarkers in IRI model

Report indicating effectiveness of device NIRs biomarkers in IRI model

Report describing MSC potency assays
RenalToolBox website

Launch of RenalToolBox website containing public information area, updated throughout the project.

RenalToolBox website set up


Firefly luciferase offers superior performance to AkaLuc for tracking the fate of administered cell therapies

Author(s): Francesco Amadeo; Francesco Amadeo; Antonius Plagge; Anitta Chacko; Anitta Chacko; Bettina Wilm; Vivien Hanson; Neill J. Liptrott; Patricia Murray; Arthur Taylor
Published in: European Journal of Nuclear Medicine and Molecular Imaging, Issue 49, 2021, Page(s) 796-808, ISSN 1619-7089
Publisher: Springer
DOI: 10.1007/s00259-021-05439-4

Endothelial Zeb2 preserves the hepatic angioarchitecture and protects against liver fibrosis

Author(s): Willeke de Haan, Wouter Dheedene, Katerina Apelt, Sofiane Décombas-Deschamps, Stefan Vinckier, Stefaan Verhulst, Andrea Conidi, Thomas Deffieux, Michael W Staring, Petra Vandervoort, Ellen Caluwé, Marleen Lox, Inge Mannaerts, Tsuyoshi Takagi, Joris Jaekers, Geert Berx, Jody Haigh, Baki Topal, An Zwijsen, Yujiro Higashi, Leo A van Grunsven, Wilfred F J van IJcken, Eskeatnaf Mulugeta, Mickael Tant
Published in: Cardiovascular Research, Issue 118(5), 2022, Page(s) 1262–1275, ISSN 1755-3245
Publisher: Oxford Academic
DOI: 10.1093/cvr/cvab148

Bioengineered Kidney Tubules Efficiently Clear Uremic Toxins in Experimental Dialysis Conditions

Author(s): Faria J, Ahmed S, Stamatialis D, Verhaar MC, Masereeuw R, Gerritsen KGF, Mihăilă SM.
Published in: International Journal of Molecular Sciences, 2023, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms241512435

A robust, accurate, sensitive LC–MS/MS method to measure indoxyl sulfate, validated for plasma and kidney cells

Author(s): Sabbir Ahmed; Rolf W. Sparidans; Jingyi Lu; Silvia M. Mihaila; Karin G. F. Gerritsen; Rosalinde Masereeuw
Published in: Biomedical Chromatography, Issue 36, 2022, Page(s) e5307, ISSN 0269-3879
Publisher: John Wiley & Sons Inc.
DOI: 10.1002/bmc.5307

Harmonised culture procedures minimise but do not eliminate mesenchymal stromal cell donor and tissue variability in a decentralised multicentre manufacturing approach

Author(s): Calcat-i-Cervera, Sandra; Rendra, Erika; Scaccia, Eleonora; Amadeo, Francesco; Hanson, Vivien; Wilm, Bettina; Murray, Patricia; O'Brien, Timothy; Taylor, Arthur; Bieback, Karen
Published in: Stem Cell Research & Therapy, Issue 14, 2023, Page(s) 120, ISSN 1757-6512
Publisher: BioMed Central
DOI: 10.1186/s13287-023-03352-1

Quantifying acute kidney injury in an Ischaemia-Reperfusion Injury mouse model using deep-learning-based semantic segmentation in histology.

Author(s): Andreea Luchian, Katherine Trivino Cepeda, Rachel Harwood, Patricia Murray, Bettina Wilm, Simon Kenny, Paola Pregel, Lorenzo Ressel
Published in: Biology Open, 2023, Page(s) bio059988, ISSN 2046-6390
Publisher: The Company of Biologists
DOI: 10.1242/bio.059988

Clinical-grade human skin-derived ABCB5+ mesenchymal stromal cells exert anti-apoptotic and anti-inflammatory effects in vitro and modulate mRNA expression in a cisplatin-induced kidney injury murine model

Author(s): Rendra, E., Crigna, A.T., Daniele, C., Sticht, C., Cueppers, M., Kluth, M.A., Ganss, C., Frank, M.H., Gretz, N., Bieback, K.
Published in: Frontiers in Immunology, 2023, ISSN 1664-3224
Publisher: Frontiers
DOI: 10.3389/fimmu.2023.1228928

Protein-Bound Uremic Toxins Induce Reactive Oxygen Species-Dependent and Inflammasome-Mediated IL-1β Production in Kidney Proximal Tubule Cells

Author(s): Mihajlovic, Milos; Krebber, Merle; Yang,Yi; Ahmed, Sabbir; Lozovanu, Valeria; Andreeva, Daria; Verhaar, Marianne; Masereeuw, Rosalinde
Published in: Biomedicines, Issue 9(10), 2021, Page(s) 1326, ISSN 2227-9059
Publisher: MDPI
DOI: 10.3390/biomedicines9101326

DEAE-Dextran Enhances the Lentiviral Transduction of Primary Human Mesenchymal Stromal Cells from All Major Tissue Sources Without Affecting Their Proliferation and Phenotype

Author(s): Francesco Amadeo, Vivien Hanson, Patricia Murray, Arthur Taylor
Published in: Molecular Biotechnology, 2022, ISSN 1073-6085
Publisher: Humana Press, Inc.
DOI: 10.1007/s12033-022-00549-2

An overview of non-invasive methods for transcutaneous measurements of glomerular filtration

Author(s): Yusuf, Mohammed M; Picascia,Tiziana; Vajpayee,Srishti; Perciaccante,Rossana; Gretz, Norbert
Published in: Journal of Experimental Nephrology, Issue 2, 2021, Page(s) 7-14, ISSN 2767-3383
Publisher: Probiologists
DOI: 10.46439/nephrology.2.008

Diabetic proximal tubulopathy: Can we mimic the disease for in vitro screening of SGLT inhibitors?

Author(s): JoãoFaria, Karin G.F.Gerritsen, Tri Q.Nguyen, Silvia M.Mihaila, RosalindeMasereeuw
Published in: European Journal of Pharmacology, Issue 908, 2021, Page(s) 174378, ISSN 0014-2999
Publisher: Elsevier BV
DOI: 10.1016/j.ejphar.2021.174378

Imaging the Renal Microcirculation in Cell Therapy.

Author(s): Katerina Apelt; Roel Bijkerk; Franck Lebrin; Franck Lebrin; Ton J. Rabelink
Published in: Cells, Issue 10(5), 2021, Page(s) 1087, ISSN 2073-4409
Publisher: MDPI
DOI: 10.3390/cells10051087

A Uremic Pig Model for Peritoneal Dialysis

Author(s): Joost C. de Vries; Maaike K. van Gelder; Anneke S. Monninkhof; Sabbir Ahmed; Diënty H. M. Hazenbrink; Tri Q. Nguyen; Gèrard A. P. de Kort; Evert-Jan P. A. Vonken; Koen R. D. Vaessen; Jaap A. Joles; Marianne C. Verhaar; Karin G. F. Gerritsen
Published in: Toxins, Issue 14(9), 2022, Page(s) 635, ISSN 2072-6651
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/toxins14090635

A simple optical tissue clearing pipeline for 3D vasculature imaging of the mediastinal organs in mice

Author(s): Quanchao Sun, Picascia Tiziana, Arif ul Maula Khan, Vincent Heuveline, Norbert Gretz
Published in: International Journal of Experimental Pathology, Issue 102, 2021, Page(s) 218-227, ISSN 0959-9673
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/iep.12399

Intravenous Administration of Human Umbilical Cord Mesenchymal Stromal Cells Leads to an Inflammatory Response in the Lung

Author(s): Hernandez Pichardo, A., Wilm, B., Liptrott, N.J., Murray, P.
Published in: Stem Cells International, 2023, ISSN 1687-9678
Publisher: Hindawi
DOI: 10.1155/2023/7397819

Adipose Stromal Cell-Derived Secretome Attenuates Cisplatin-Induced Injury In Vitro Surpassing the Intricate Interplay between Proximal Tubular Epithelial Cells and Macrophages

Author(s): Rendra, E., Uhlig, S., Moskal, I., Thielemann, C., Klueter, H., Bieback, K
Published in: Cells, 2024, ISSN 2073-4409
Publisher: MDPI
DOI: 10.3390/cells13020121

Mesenchymal stromal cells secretome restores bioenergetic and redox homeostasis in human proximal tubule cells after ischemic injury

Author(s): João Faria, Sandra Calcat-i-Cervera, Renata Skovronova, Bonnie C. Broeksma, Alinda J. Berends, Esther A. Zaal, Benedetta Bussolati, Timothy O’Brien, Silvia M. Mihăilă, Rosalinde Masereeuw
Published in: Stem Cell Research & Therapy, 2023, ISSN 1757-6512
Publisher: BioMed Central
DOI: 10.1186/s13287-023-03563-6

The Influence of OAT1 Density and Functionality on Indoxyl Sulfate Transport in the Human Proximal Tubule: An Integrated Computational and In Vitro Study

Author(s): King, Jasia; Mihaila, Silvia; Ahmed, Sabbir; Truckenmüller, Roman; Giselbrecht, Stefan; Masereeuw, Rosalinde; Carlier, Aurélie
Published in: Toxins, Issue 13(10), 2021, Page(s) 674, ISSN 2072-6651
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/toxins13100674

Mesenchymal stromal cells: what have we learned so far about their therapeutic potential and mechanisms of action?

Author(s): Francesco Amadeo; Katherine Trivino Cepeda; James Littlewood; Bettina Wilm; Arthur Taylor; Patricia Murray
Published in: Emerging Topics in Life Sciences, Issue 5(4), 2021, Page(s) 549-562, ISSN 2397-8562
Publisher: Portland Press
DOI: 10.1042/etls20210013

Umbilical cord mesenchymal stromal cell-derived extracellular vesicles lack the potency to immunomodulate human monocyte-derived macrophages in vitro

Author(s): Tamiris Borges da Silva, Erika Rendra, Christopher A.W. David, Karen Bieback, Michael J. Cross, Bettina Wilm, Neill J. Liptrott, Patricia Murray,
Published in: Biomedicine & Pharmacotherapy, 2023, Page(s) 115624, ISSN 0753-3322
Publisher: Elsevier Masson
DOI: 10.1016/j.biopha.2023.115624

Adipose stromal cells bioproducts as cell-free therapies: manufacturing and therapeutic dose determine in vitro functionality

Author(s): Skovronova, R., Scaccia, E., Calcat-i-Cervera, S., Bussolati, B., O’Brien, T. & Bieback, K
Published in: Journal of Translational Medicine, 2023, ISSN 1479-5876
Publisher: BioMed Central
DOI: 10.1186/s12967-023-04602-9

Fate of intravenously administered umbilical cord mesenchymal stromal cells and interactions with the host's immune system

Author(s): Francesco Amadeo, Vivien Hanson, Neill J. Liptrott, Bettina Wilm, Patricia Murray, Arthur Taylor
Published in: Biomedicine & Pharmacotherapy, Issue 159, 2023, Page(s) 114191, ISSN 0753-3322
Publisher: Elsevier Masson
DOI: 10.1016/j.biopha.2022.114191

Human platelet lysate-derived extracellular vesicles enhance angiogenesis through miR-126

Author(s): Antonella Bordin, Maila Chirivì, Francesca Pagano, Marika Milan, Marco Iuliano, Eleonora Scaccia, Orazio Fortunato, Giorgio Mangino, Xhulio Dhori, Elisabetta De Marinis, Alessandra D'Amico, Selenia Miglietta, Vittorio Picchio, Roberto Rizzi, Giovanna Romeo, Fabio Pulcinelli, Isotta Chimenti, Giacomo Frati, Elena De Falco
Published in: Cell Proliferation, Issue 55, 2022, Page(s) e13312, ISSN 0960-7722
Publisher: Blackwell Publishing Inc.
DOI: 10.1111/cpr.13312

Optical Tissue Clearing to Study the Intra-Pulmonary Biodistribution of Intravenously Delivered Mesenchymal Stromal Cells and Their Interactions with Host Lung Cells

Author(s): Alejandra Hernandez Pichardo; Francesco Amadeo; Bettina Wilm; Raphaël Lévy; Lorenzo Ressel; Patricia Murray; Violaine Sée
Published in: International Journal of Molecular Sciences, Issue 23, 2022, Page(s) 14171, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms232214171

Application of ethyl cinnamate based optical tissue clearing and expansion microscopy combined with retrograde perfusion for 3D lung imaging

Author(s): Quanchao Sun, Tiziana Picascia, Arif ul Maula Khan, Cinzia Brenna, Vincent Heuveline, Anja Schmaus, Jonathan P. Sleeman, Norbert Gretz
Published in: Experimental Lung Research, 2020, Page(s) 1-16, ISSN 0190-2148
Publisher: Taylor & Francis
DOI: 10.1080/01902148.2020.1829183

Surface Marker Expression in Small and Medium/Large Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Naive or Apoptotic Condition Using Orthogonal Techniques

Author(s): Skovronova Renata; Grange Cristina; Dimuccio Veronica; Deregibus Maria Chiara; Camussi Giovanni; Bussolati Benedetta
Published in: Cells, Issue 10(11), 2021, Page(s) 2948, ISSN 2073-4409
Publisher: MDPI
DOI: 10.3390/cells10112948

Stem Cell-Derived Extracellular Vesicles and Kidney Regeneration

Author(s): Grange, Skovronova, Marabese, Bussolati
Published in: Cells, Issue 8/10, 2019, Page(s) 1240, ISSN 2073-4409
Publisher: MDPI
DOI: 10.3390/cells8101240

Kidney-based in vitro models for drug-induced toxicity testing

Author(s): João Faria, Sabbir Ahmed, Karin G. F. Gerritsen, Silvia M. Mihaila, Rosalinde Masereeuw
Published in: Archives of Toxicology, Issue 93/12, 2019, Page(s) 3397-3418, ISSN 0340-5761
Publisher: Springer Verlag
DOI: 10.1007/s00204-019-02598-0

Recent advances in understanding mesenchymal stromal cells

Author(s): Erika Rendra, Eleonora Scaccia, Karen Bieback
Published in: F1000Research, Issue 9, 2020, Page(s) 156, ISSN 2046-1402
Publisher: F1000 Research Ltd.
DOI: 10.12688/f1000research.21862.1

Extracellular Vesicles Derived from Induced Pluripotent Stem Cells Promote Renoprotection in Acute Kidney Injury Model

Author(s): Federica Collino, Jarlene A. Lopes, Marta Tapparo, Giovane G. Tortelote, Taís H. Kasai-Brunswick, Gustavo M.C. Lopes, Douglas B. Almeida, Renata Skovronova, Camila H. C. Wendt, Kildare R. de Miranda, Benedetta Bussolati, Adalberto Vieyra, Rafael Soares Lindoso
Published in: Cells, Issue 9/2, 2020, Page(s) 453, ISSN 2073-4409
Publisher: MDPI
DOI: 10.3390/cells9020453

Extracellular Vesicles, Apoptotic Bodies and Mitochondria: Stem Cell Bioproducts for Organ Regeneration

Author(s): Natalia Gebara, Andrea Rossi, Renata Skovronova, Justine Mariam Aziz, Amish Asthana, Benedetta Bussolati
Published in: Current Transplantation Reports, Issue 7/2, 2020, Page(s) 105-113, ISSN 2196-3029
Publisher: Springer
DOI: 10.1007/s40472-020-00282-2

Animal Models for Studying Protein-Bound Uremic Toxin Removal—A Systematic Review

Author(s): Ahmed S, de Vries JC, Lu J, Stuart MHV, Mihăilă SM, Vernooij RWM, Masereeuw R, Gerritsen KGF
Published in: International Journal of Molecular Sciences, 2023, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms241713197

When Origin Matters: Properties of Mesenchymal Stromal Cells From Different Sources for Clinical Translation in Kidney Disease

Author(s): Sandra Calcat-i-Cervera, Clara Sanz-Nogués and Timothy O'Brien
Published in: Frontiers in Medicine, Issue 8, 2021, ISSN 2296-858X
Publisher: Frontiers
DOI: 10.3389/fmed.2021.728496

Organs-on-chip technology: a tool to tackle genetic kidney diseases

Author(s): Marta G. Valverde, João Faria, Elena Sendino Garví, Manoe J. Janssen, Rosalinde Masereeuw & Silvia M. Mihăilă
Published in: Pediatric Nephrology, Issue 37, 2022, Page(s) 2985–2996, ISSN 0931-041X
Publisher: Springer Verlag
DOI: 10.1007/s00467-022-05508-2

Drugs Commonly Applied to Kidney Patients May Compromise Renal Tubular Uremic Toxins Excretion

Author(s): Silvia M. Mihaila, João Faria, Maurice F. J. Stefens, Dimitrios Stamatialis, Marianne C. Verhaar, Karin G. F. Gerritsen, Rosalinde Masereeuw
Published in: Toxins, Issue 12/6, 2020, Page(s) 391, ISSN 2072-6651
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/toxins12060391

Multispectral optoacoustic tomography is more sensitive than micro-computed tomography for tracking gold nanorod labelled mesenchymal stromal cells

Author(s): Alejandra Hernandez Pichardo, James Littlewood, Arthur Taylor, Bettina Wilm, Raphaël Lévy, Patricia Murray
Published in: Journal of Biophotonics, 2023, Page(s) e202300109, ISSN 1864-063X
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/jbio.202300109

Human Cholangiocytes Form a Polarized and Functional Bile Duct on Hollow Fiber Membranes

Author(s): Zhenguo Wang; João Faria; Luc J. W. van der Laan; Louis C. Penning; Rosalinde Masereeuw; Bart Spee
Published in: Frontiers in Bioengineering and Biotechnology, Issue 10, 2022, Page(s) 868857, ISSN 2296-4185
Publisher: Frontiers Media
DOI: 10.3389/fbioe.2022.868857

New technical approaches for 3D morphological imaging and quantification of measurements

Author(s): Cinzia Brenna, Arif ul Maula Khan, Tiziana Picascia, Quanchao Sun, Vincent Heuveline, Norbert Gretz
Published in: The Anatomical Record, Issue 303/10, 2020, Page(s) 2702-2715, ISSN 1932-8486
Publisher: John Wiley & Sons Inc.
DOI: 10.1002/ar.24463

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